lncRNA Xist Regulates Osteoblast Differentiation by Sponging miR-19a-3p in Aging-induced Osteoporosis

Chen, Shijie; Li, Yuezhan; Zhi, Shuang; Ding, Zhiyu; Huang, Yan; Wang, Weiguo; Zheng, Ruping; Yu, Haiyang; Wang, Jianlong; Hu, Minghua; Miao, Jun; Li, Jinsong

doi:10.14336/ad.2019.0724

Cited by 58 publications

(33 citation statements)

References 42 publications

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“…Elevated miR-19a-3p expression is associated with the potential of lymph node metastasis ( 34 , 35 ). Moreover, recent study highlighted the positive role of miR-19a-3p in osteoblast differentiation by targeting Hoxa5 ( 36 ). However, the role of miR-19a-3p in osteoclastogenesis remains poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Osteosarcoma Cell-Derived Small Extracellular Vesicles Enhance Osteoclastogenesis and Bone Resorption Through Transferring MicroRNA-19a-3p

et al. 2021

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Osteosarcoma (OS) is the most common primary bone cancer characterized by an aggressive phenotype with bone destruction. The prognosis of OS patients remains unoptimistic with the current treatment strategy. Recently, osteoclasts are believed to play a crucial role in cancer bone metastasis. Thus, osteoclast could be a target both in bone destruction and cancer progression in OS. However, mechanisms governing osteoclastogenesis in OS remain poorly understood. miRNA delivered by small extracellular vesicles (sEVs) could mediate cellular communications. In this study, we investigated the effects of sEVs on osteoclastogenesis and osteoclast function, also clarified the underlying mechanism. We herein found that sEVs promoted pre-osteoclast migration, osteoclastogenesis and resorption by exposing RAW264.7 cells to sEVs derived from OS cells. Bioinformatics analysis showed that phosphatase tension homologue (PTEN), and miR-19a-3p were involved in OS progression. Overexpression of miR-19a-3p or sEVs’ miR-19a-3p promoted osteoclast formation and function through PTEN/PI3K/AKT signaling pathway, while inhibition of miR-19a-3p showed the contrary results. The bone marrow macrophages (BMMs) were used to verify the results. OS mice, which were established by subcutaneous injection of OS cells, exhibited increased levels of sEVs’ miR-19a-3p in blood. Moreover, micro-computed tomography (CT) and histomorphometry analysis demonstrated that OS mice exhibited osteopenia with increased number of osteoclasts. In conclusion, miR-19a-3p delivery via OS cell-derived sEVs promotes osteoclast differentiation and bone destruction through PTEN/phosphatidylinositol 3 -kinase (PI3K)/protein kinase B (AKT) signaling pathway. These findings highlight sEVs packaging of miR-19a-3p as a potential target for prevention and treatment of bone destruction and cancer progression in OS patients. And this finding provides a novel potentially therapeutic target for the bone metastasis.

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Section: Discussionmentioning

confidence: 99%

Osteosarcoma Cell-Derived Small Extracellular Vesicles Enhance Osteoclastogenesis and Bone Resorption Through Transferring MicroRNA-19a-3p

et al. 2021

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“…eskildsen et al (11) showed that mirna-138 was related to the osteogenic differentiation of hMScs and that the overexpression of mir-138 inhibited the oB differentiation of hMScs. The lncrna Xist was found to sponge mir-19a-3p to repress BMSc osteogenic differentiation in ageing-induced osteoporosis (12). owing to the development of deep sequencing technology, an increasing number of biologically significant ncRNAs affecting bone metabolism and osteoporosis have been studied.…”

Section: Effects Of Mirnas Lncrnas and Circrnas On Osteoporosis As Regulatory Factors Of Bone Homeostasis (Review)mentioning

confidence: 99%

“…The switch between the adipogenic and osteogenic differentiation of BMScs plays an important role in ageing-induced osteoporosis. mir-19a-3p is able to regulate oB differentiation in BMScs by regulating Hoxa5 expression, and lncrna Xist, as a sponge of mir-19a-3p, plays a crucial role in oB differentiation by binding mir-19a-3p in BMScs (12). recently, Zhang et al (53) found that the expression of the lncrna loXl1-aS1 was high in the peripheral blood from patients with osteoporosis and that this gradually decreased during the process of osteogenic differentiation of hBMScs.…”

Section: Mechanisms By Which Ncrnas Regulate Bmscs In Osteoporosismentioning

confidence: 99%

“…Similarly, niu et al (121) revealed that XiST, which was found to be upregulated in plasma, also promoted oB apoptosis through the mir-203-3p/ZFPM2 pathway. in addition, XiST plays a role in regulating oB differentiation by modulating the expression of mir-19a-3p, indicating that XiST performs various important regulatory functions in bone-related diseases (12). The effect of lncrna-mediated autophagy on oBs in osteoporosis has rarely been reported and needs further exploration (Table V).…”

Section: Effects Of Lncrnas On Regulation Of Obsmentioning

confidence: 99%

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Effects of miRNAs, lncRNAs and circRNAs on osteoporosis as regulatory factors of bone homeostasis (Review)

Han

Tan

et al. 2021

Mol Med Rep

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osteoporosis is a common metabolic bone disorder typically characterized by decreased bone mass and an increased risk of fracture. at present, the detailed molecular mechanism underlying the development of osteoporosis remains to be elucidated. accumulating evidence shows that non-coding (nc)rnas, such as micrornas (mirnas), long ncrnas (lncrnas) and circular rnas (circRNAs), play significant roles in osteoporosis through the post-transcriptional regulation of gene expression as regulatory factors. Previous studies have demonstrated that ncrnas participate in maintaining bone homeostasis by regulating physiological and developmental processes in osteoblasts, osteoclasts and bone marrow stromal cells. in the present review, the latest research investigating the involvement of mirnas, lncrnas and circrnas in regulating the differentiation, proliferation, apoptosis and autophagy of cells that maintain the bone microenvironment in osteoporosis is summarized. deeper insight into the aspects of osteoporosis pathogenesis involving the deregulation of ncrnas could facilitate the development of therapeutic approaches for osteoporosis. Contents 1. introduction 2. Mechanisms by which ncrnas regulate BMScs in osteoporosis 3. Mechanisms by which ncrnas regulate oBs in osteoporosis 4. Mechanisms by which ncrnas regulate ocs in osteoporosis 5. conclusion and perspectives

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“…lncRNAs have been found to participate in the pathogenesis related to PD by regulating neuroinflammation, oxidative stress ( Bu et al, 2020 ), cell cycle, mitochondrial dysfunction, and amyloid β (Aβ) production ( Chen Y. et al, 2019 ; Gao et al, 2020 ). In addition, lncRNA Xist regulates osteoblast differentiation by sponging miR-19a-3p in aging-induced osteoporosis of bone marrow mesenchymal stem cells ( Chen et al, 2020 ). A recent profiling study also showed that many lncRNAs were significantly altered in peripheral blood of depressed patients ( Cui et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Integrative Analysis of lncRNA and mRNA and Profiles in Postoperative Delirium Patients

Song

Wang²,

Hou³

et al. 2021

Front. Aging Neurosci.

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Delirium is a common serious complication that often occurs after major surgery. The goals of this study were to explore the expression profiles and functional networks of long non-coding RNAs (lncRNAs) and mRNAs in patients of postoperative delirium (POD). Microarray analysis was performed on the peripheral blood samples to identify differentially expressed (DE) lncRNAs and mRNAs in 4 POD patients and 4 non-POD volunteers. DE lncRNAs and mRNAs were validated by quantitative reverse transcription PCR (RT-qPCR). Bioinformatic analyses were performed to identify the critical biological functions and signaling pathways involved in POD. A total of 1195 DE lncRNAs and 735 DE mRNAs were identified between the POD and non-POD groups. Verified by the RT-qPCR, we identified 14 DE lncRNAs that may relate to the pathogenesis of POD. These 14 DE lncRNAs play important regulatory roles in “glutamate and 5-hydroxytryptamine,” “synaptotagmin 7,” “transient receptor potential channel,” “interleukin-2 production.” There was a regulatory relationship between lncRNA ENST00000530057 and synaptotagmin (Syt) 7 mRNA. The mRNA level of PCLO was up-regulated in POD group. This study showed abundant DE lncRNAs and mRNAs in POD that might help in deciphering the disease pathogenesis.

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lncRNA Xist Regulates Osteoblast Differentiation by Sponging miR-19a-3p in Aging-induced Osteoporosis

Cited by 58 publications

References 42 publications

Osteosarcoma Cell-Derived Small Extracellular Vesicles Enhance Osteoclastogenesis and Bone Resorption Through Transferring MicroRNA-19a-3p

Osteosarcoma Cell-Derived Small Extracellular Vesicles Enhance Osteoclastogenesis and Bone Resorption Through Transferring MicroRNA-19a-3p

Effects of miRNAs, lncRNAs and circRNAs on osteoporosis as regulatory factors of bone homeostasis (Review)

Integrative Analysis of lncRNA and mRNA and Profiles in Postoperative Delirium Patients

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